Alcohol use disorders are nearly as common among older adolescents as among adults. Adolescents who abuse alcohol or are dependent on alcohol often manifest impulsive, aggressive, and antisocial behaviors. A study in the November issue of Alcoholism: Clinical & Experimental Research examines the possibility that variations in brain chemistry can ‘set the stage’ for risk-taking behaviors. More specifically, it studies the role that dysregulation of central serotonergic function may play in impulsiveness, aggression, and conduct disorders in older adolescents (between 16 and 21 years of age) with alcohol problems.
"Impulsive and aggressive personality traits, as well as impulsive-aggressive behavior," explained Paul H. Soloff, professor of psychiatry at the University of Pittsburgh School of Medicine and lead author of the study," are temperamental traits that lead to socially disinhibited behavior, also called ‘behavior undercontrol.’ Kids with behavior undercontrol are more likely to develop alcohol use disorders than non-impulsive-aggressive kids."
One type of adult alcoholism, referred to as Type II, is defined by antisocial behavior, including many expressions of behavior undercontrol, as well as early onset (before age 25), and male predominance. (This is in contrast to Type I alcoholism, which is found in both males and females, occurs later in life, and is not associated with antisocial traits.) Research suggests that there is a biologic (and possibly hereditary) basis for the temperament of impulsivity that is related to dysregulation of the neurotransmitter serotonin in the parts of the brain that inhibit impulses. Studies of adults with alcohol use disorders have found evidence of decreased serotonin function, especially those with Type II alcoholism (identified by antisocial behavior). Similarly, studies of impulsive-aggressive individuals, independent of alcohol use disorders, have found diminished serotonin function.
"We looked at adolescents who already had developed alcohol use disorders," said Soloff, "to see if they had higher levels of impulsivity and aggressivity than healthy control subjects, and to also see if they had lower central serotonergic function. We measured central serotonin function by giving them a single dose of a medicine called fenfluramine, which releases serotonin in the brain, and then looked for effects of that release in the blood." Serotonin itself cannot be measured in the blood. However, serotonin release in the brain causes a rise in the hormones prolactin and cortisol in the blood. The changes in prolactin and cortisol provided an index of serotonin responsiveness.
"In adults with alcohol use disorders," said Duncan B. Clark, director of the Pittsburgh Adolescent Alcohol Research Center, "the serotonin system is relatively insensitive or unresponsive to stimulation. In this study, the serotonin responsivity results were somewhat different than would be expected from studies of adults."
Neither Soloff nor Clark were surprised that older adolescents with alcohol use disorders had more impulsivity and aggressivity than control subjects. The boys tended to be more aggressive in general than the girls, but both had equally high levels of impulsivity. Furthermore, overall the two groups (alcohol users and control subjects) did not significantly differ on their prolactin or cortisol responses. This suggests that not all youth with significant alcohol use disorders early in life have a dysregulation of serotonin metabolism. However, the most ‘extreme subjects’ – nine boys with both alcohol use disorders and the most antisocial traits (which were diagnosed as conduct disorder) – had a significant elevation in cortisol response, which correlated with measures of aggressivity.
"These findings may be interpreted to show that the serotonin system was more responsive in these subjects," said Clark. "[This may reflect] an earlier stage of neurobiological development. Increased responsiveness of the serotonin system in adolescence may be followed by decreased responsiveness in adulthood. However, the level of responsiveness may not be as important as the ability of the brain to regulate the response to stimulation. While not in the same direction as with adults, these results are still consistent with the idea that individuals with these high-risk behaviors have serotonin dysregulation."
Soloff concurs, although he readily points out the interpretative limitations of studying small numbers of subjects. "In light of previous work done on aggressive young children, some of whom have an increased serotonin response, and aggressive adults, who generally have a diminished response, our findings suggest that the elevation of cortisol in adolescents with alcohol use disorders and conduct disorder – which reflects an increased effect of serotonin – may herald a gradual loss of serotonin responsiveness by adulthood."
Soloff plans to further study the serotonin system using positron emission tomography (PET) neuroimaging, where metabolic changes can be "visualized." He believes this research will ultimately reveal more about where in the brain impulsivity is controlled, how serotonin is regulated in these individuals, and whether this dysregulation can be remedied.
"This area of research is important to advance our understanding of how brain chemistry may influence problem alcohol involvement and violent behavior," noted Clark. "We need to know more about the development of the serotonin system from childhood through adolescence and into adulthood. New brain imaging techniques may allow us to study brain chemistry directly rather than relying on measurement of effects of brain chemistry on blood chemistry. Through an understanding of the brain and behavior, better approaches to identifying children at risk, better prevention programs, and more effective treatment interventions may be developed."